Neuronal Stimulant Actions of Prostacyclin and its Novel Mimetics

Prostacyclin stimulates sensory nerve endings or autonomic motor neurones in a number of tissues. Activation of prostacyclin (IP-) receptors appears to be involved since similar effects are produced by cicaprost (Figure 1), a highly potent and selective IP-receptor agonist (Dong et al., 1986). We have recently studied the actions of IP-receptor agonists on two isolated preparations, the rat colon and the guinea-pig vas deferens. In the former, cicaprost inhibits spontaneous contractile activity by releasing inhibitory transmitters from non-adrenergic non-cholinergic (NANC) enteric nerves (Qian and Jones, 1995). This action is partially inhibited by the nitric oxide synthase (NOS) inhibitor L-NAME (but not by D-NAME), indicating release of NO. The residual inhibition is abolished by apamin, indicating that a second transmitter probably activates receptors which open calcium-activated K+-channels in the pacemaker and/or smooth muscle cell membranes. The nature of this transmitter has not been defined, but it is unlikely to be adenosine, ATP, VIP (Qian and Jones, 1995) or PACAP (unpublished observations).